Paroxysmal Hemicrania

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••Chapter 97

◗ Paroxysmal Hemicrania

Christopher J. Boes, Maurice Vincent, and David Russell

PAROXYSMAL HEMICRANIA Sex Distribution PH was originally considered to be a female disease. Male International Headache Society (IHS) code and diag- cases, however, clearly occur (46,48). In initial series there nosis: was a female:male ratio of 7:1, but a 1989 review re- 3.2 Paroxysmal hemicrania ported a female:male ratio of 2.36:1 (1). Comprehensive 3.2.1 Episodic paroxysmal hemicrania and methodologically well-designed epidemiologic stud- 3.2.2 Chronic paroxysmal hemicrania ies are required to establish the actual extent of the female World Health Organization (WHO) code and diagnosis: preponderance in PH. G44.03 Chronic paroxysmal hemicrania Short description: Paroxysmal hemicrania (PH) sufferers have attacks with similar characteristics of pain Age of Onset and associated symptoms and signs to those of cluster PH may begin at any time, but its onset usually occurs headache (CH), but they are shorter lasting, are more during adulthood at the mean age of 34 years. The youngest frequent, occur more commonly in females, and re- age at onset was 1 year and the oldest 81 years (1,12). In spond absolutely to indomethacin. In episodic paroxys- the reviewed material from 1989, the mean age at diagnosis mal hemicrania (EPH), attacks occur in periods lasting was 47 and the mean illness duration 13 years. As far as 7 days to 1 year separated by pain-free periods lasting the subtypes are concerned, EPH seems to begin earlier 1 month or longer. In chronic paroxysmal hemicrania (mean 27 years) than CPH (mean 37 years) (1). (CPH), attacks occur for more than 1 year without remission or with remissions lasting less than 1 month (21). GENETICS Other terms: Sjaastad syndrome There is no evidence of a genetic etiology in PH. Parents EPIDEMIOLOGY or siblings do not have an increased incidence of CH or migraine compared with the general population (1). PH is a relatively rare disorder. Data on PH epidemiology are scarce, and many cases are probably still overlooked. Following the original description (58), new patients have ANATOMY, PATHOLOGY, been identiﬁed in several countries (1,25,57) and isolated AND PATHOPHYSIOLOGY PH cases are no longer reported. The incidence and prevalence of PH are not known, but the relative frequency com- The pathogenesis of PH remains unknown. The unilateral- pared to CH is reported to be approximately 1 to 3% (1). ity and pain intensity, as well as the autonomic symptoms Prevalence estimates in CH vary from 56 per 100,000 to 381 and signs, suggest that some mechanisms may be shared per 100,000 (51,61,69). It has been reported that the preva- with the other trigeminal autonomic cephalalgias (TACs) lence of CH in the United States, based on one large study, listed in group 3 of the 2004 IHS headache classiﬁcation. was 401 per 100,000 (51). However, this was a U.S. study The absolute indomethacin effect, however, indicates that of CH incidence, not prevalence, and converting incidence PH has a distinct pathophysiology. In most of the cases no to prevalence estimates is naturally combined with un- underlying pathology is detected by any supplementary in- certainties because survival time needs to be conjectured vestigation. Several secondary cases, however, have been (61,68). described (70) (Table 97-1).

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816 Tension-Type Headaches, Cluster Headaches, and Other Primary Headaches

◗ TABLE 97-1 Secondary Paroxysmal Hemicrania ular blood flow (23). The pulse synchronous changes in IOP are reflected by the corneal indentation pulse (CIP) ■ Vascular amplitudes, which may be measured in micrometers by ■ Circle of Willis aneurysm dynamic tonometry (22). The corresponding changes in ■ Occipital, middle cerebral artery infarctions intraocular volume in cubic milliliters can be estimated ■ Parietal arteriovenous malformation ■ Tumor using conversion tables. In PH there is a significant attack- ■ Malignant frontal tumor related increase in CIP amplitudes, ocular blood flow, and ■ Cavernous sinus meningioma IOP that is bilateral but more pronounced on the symp- ■ Petrous ridge meningioma tomatic side (55). The attack-related increase in IOP can- ■ Gangliocytoma of the sella turcica not be solely explained by changes in aqueous humor dy- ■ Pituitary adenoma namics because the increased volume exceeds turnover ■ Parotid epidermoid metastases of aqueous humor and the IOP changes occur so rapidly ■ Pancoast tumor (<30 seconds). Therefore, these findings are probably the ■ Miscellaneous result of an acute vasodilation that increases intraocular ■ Collagen vascular disease volume due to a neurogenic impulse and vasoactive neu- ■ Intracranial hypertension ropeptide release (55). ■ Maxillary cyst ■ Ophthalmic herpes zoster Since changes in IOP and CIP may indicate local abnor- ■ Essential thrombocythemia mal hemodynamics, spontaneous PH attacks were studied ■ Posttraumatic with transcranial Doppler (54). During attacks, there was hyperventilation, reduction of the end-tidal PCO2, and de- From refs. 5, 33, 70. crease in blood flow velocity in all insonated arteries, on both symptomatic and nonsymptomatic sides. In the ante- rior cerebral artery, the reduction was significantly smaller Although the pain in PH is strictly unilateral, autonomic on the symptomatic side. There was no major difference involvement and ocular signs may be bilateral, albeit more between patients and controls considering reduction of pronounced on the symptomatic side. The existence of bi- flow during hypocapnia, indicating that vascular reactivity lateral ocular signs seems to exclude the possibility of a in PH is normal. single lesion of the peripheral nervous system being the Corneal temperature has been found to be increased on cause of PH. A central lesion involving midline structures the symptomatic side during attacks, a finding that may seems therefore more probable (e.g., hypothalamus, cav- also be due to increased ocular blood flow following va- ernous sinus) (40,56). Functional neuroimaging studies sodilation (13). have shown specific activation of hypothalamic areas in The abruptness with which the accompanying au- some TACs, including CH and SUNCT (short-lasting uni- tonomic signs occur in mechanically precipitated at- lateral neuralgiform headache attacks with conjunctival tacks suggests that they may be mediated by neurogenic injection and tearing) syndrome (35,36,67). Similar neu- impulses. This would involve neuropeptide-containing roimaging findings in PH are not available. perivascular fibers of the trigeminovascular system with The pain in PH cannot be explained by a disturbance its connections to the cavernous sinus plexus and brain- in the autonomic nervous system alone. This is based on stem. The release of vasoactive peptides from sensory the observation that autonomic signs may precede the de- fibers, which run in close relationship to other autonomic velopment of pain in precipitated attacks and that the fibers, may also lead to miosis, increased IOP, and other pharmacologic suppression of autonomic signs does not autonomic disturbances observed in PH (14,37). Calci- influence the pain pattern during attacks (66). Besides, tonin gene–related peptide (CGRP), a peptide released the clinical picture does not fit with any classic sympa- from trigeminal fibers, and vasoactive intestinal polypep- thetic or parasympathetic syndrome. The pathophysio- tide (VIP), a parasympathetic peptide, have been found to logic mechanisms responsible for the pain in PH remain be abnormally high during a PH attack (18). Values re- unknown. It has been suggested that the ipsilateral distri- turned to basal levels following indomethacin treatment. bution of trigeminal fibers in the trigeminovascular system This is similar to the peptides’ profile found in CH (17), may explain the unilaterality of the pain, and evidence of suggesting that this disorder and PH may share patho- trigeminal–parasympathetic activation during PH attacks physiologic traits to a certain extent. It is possible that has emerged (18). the clinical picture in PH results from the interaction be- The ocular findings in PH patients have been studied in tween neurotransmitters and neuromodulators released detail with dynamic tonometry (22,23). Pulse synchronous from sympathetic, parasympathetic, and sensory fibers changes in intraocular pressure (IOP) may be recorded. at the frontal area and local autonomic and vascular They depend on the volume of the pulsatile part of oc- mediators. 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Paroxysmal Hemicrania 817

The ocular vascular findings (increased IOP, conjuncti- The mechanism behind precipitation of attacks may val injection) may also be explained by autonomic changes. theoretically be due to reflex mechanisms involving con- The situation seems to be more intricate since experiments nections between the trigeminovascular system and brain- show that the IOP increase is inhibited by an α-blocking stem. However, local pathologic findings in the neck struc- agent (thymoxamine) as well as satellite ganglion blockade tures have not been found. (66). This observation, together with increased sweating In conclusion, the pathologic mechanisms behind the and decreased salivation on the symptomatic side during PH syndrome are incompletely understood. However, PH attacks, suggests sympathetic stimulation (52,53). The based on the available information, the occurrence of both sweat abnormality observed in some patients (53,64,65) unilateral and bilateral symptoms may suggest a primary suggests a direct sympathetic stimulation rather than a su- central triggering mechanism and a secondary involve- persensitivity reaction, which has been found in CH (64). ment of peripheral factors probably mediated by neuro- Increased tearing, nasal secretion, and miosis may, on the genic impulses. other hand, be due to a parasympathetic stimulation during attacks (52). Heart rate and electrocardiogram (ECG) changes dur- CLINICAL FEATURES ing attacks show no typical pattern and differ therefore from those observed during CH attacks (50). There is, how- IHS diagnostic criteria for PH (21): ever, a tendency to marked variations in heart rate in as- A. At least 20 attacks fulfilling criteria B through D sociation with attacks of PH. Attack-related heart rhythm B. Attacks of severe, unilateral orbital, supraorbital, or disturbances have been observed in some patients: brady- temporal pain lasting 2 to 30 minutes cardia and sinoatrial block, bundle branch block with C. Headache is accompanied by at least one of the follow- episodes of atrial fibrillation, multiple extrasystoles, and ing: bradycardia (50). These findings may indicate a dysfunc- 1. Ipsilateral conjunctival injection and/or lacrimation tion in the central control of the autonomic nervous system 2. Ipsilateral nasal congestion and/or rhinorrhea during PH attacks. 3. Ipsilateral eyelid edema Pain pressure threshold (PPT), the nociceptive flexion 4. Ipsilateral forehead and facial sweating reflex (RIII), corneal reflex, and blink reflex have been stud- 5. Ipsilateral miosis and/or ptosis ied in a few PH cases (2). The PPT and the subjective pain D. Attacks have a frequency >5 per day for more than half perception following sural nerve stimulation were reduced of the time, although periods with lower frequency may in PH, as was the RIII reflex threshold on the symptomatic occur. side as compared to controls. Blink reflexes were normal, E. Attacks are prevented completely by therapeutic doses and the corneal reflex thresholds were reduced bilaterally, of indomethacin (see Notes). irrespective of indomethacin intake. Interestingly, the RIII F. Not attributed to another disorder (see Notes) threshold was not affected by indomethacin, but the subjective pain perception was significantly more asymmetric Notes: in PH on the drug than in controls. 1. To rule out incomplete response, indomethacin should be used in a dose of at least 150 mg daily orally or rec- The Indomethacin Effect tally, or at least 100 mg by injection, but for mainte- The mechanism behind the absolute indomethacin effect nance smaller doses are often sufficient. and the reason why equipotent cyclooxygenase inhibitors 2. History and physical and neurologic examinations do are not as effective remain unknown. It does not seem not suggest any of the disorders listed in groups 5 to to be due to its effect on prostaglandin synthesis, since 12, or history and/or physical and/or neurologic exam- other nonsteroidal antiinflammatory drugs (NSAIDs) with inations do suggest such disorder but it is ruled out by an even more potent antiprostaglandin action have little or appropriate investigations, or such disorder is present no effect in PH. Both indomethacin and acetylsalicylic acid but attacks do not occur for the first time in close tem- block neurogenic inflammation (9). Indomethacin reduces poral relation to the disorder. cerebral blood flow (71), but its effect on peptide-induced vasodilation of isolated ophthalmic arteries is no different IHS diagnostic criteria for EPH (21): than other NSAIDs. It is possible that indomethacin af- A. Attacks fulfilling criteria A to F for 3.2 Paroxysmal hem- fects vessels via a nonprostaglandin-related phenomenon icrania (16,47). The indomethacin effect seems to be symptomatic B. At least two attack periods lasting 7 to 365 days rather than curative, since symptoms recur after the dis- and separated by pain-free remission periods of ≥1 continuation of the drug. month P1: KWW/KKL P2: KWW/HCN QC: KWW/FLX T1: KWW GRBT050-97 Olesen- 2057G GRBT050-Olesen-v6.cls August 17, 2005 1:30

818 Tension-Type Headaches, Cluster Headaches, and Other Primary Headaches

IHS diagnostic criteria for CPH (21): in late 1972 we finally arrived at indomethacin on our A. Attacks fulfilling criteria A to F for 3.2 Paroxysmal hem- list, the response was no less than miraculous” (57). icrania B. Attacks recur for >1 year without remission periods or A remitting form of the disease was subsequently rec- with remission periods lasting <1 month. ognized and termed episodic paroxysmal hemicrania (28). The IHS gave diagnostic criteria for CPH in 1988 (20), and in 2004 the IHS classified CPH and EPH as subtypes of History paroxysmal hemicrania (21). Sjaastad and Dale reported a new treatable headache entity in 1974 (58), and in 1976 they named the entity chronic Headache Phenotype paroxysmal hemicrania (59). The first case seen by Sjaas- tad was described in detail in his book Cluster Headache Patients with PH typically have unilateral, brief, severe at- Syndrome and will be quoted extensively because of its im- tacks of pain associated with cranial autonomic features portance (57). that recur several times per day. The pain is most often in a V1 distribution, but it can be extratrigeminal. In An- “The first case of chronic paroxysmal hemicrania tonaci and Sjaastad’s retrospective review of 84 CPH pa- (CPH), a female aged 44 years with a 9-year history tients, the maximal pain was most often in the ocular, tem- of headache, was brought to our cognizance in 1961, with a diagnosis of ‘typical cluster headache.’ However, poral, maxillary, or forehead areas (1). It was less often in the patient was a female (which, of course, may be con- the neck/shoulder, retroocular, or occipital regions (1). The sistent with a diagnosis of ordinary cluster headache, quality of pain is usually clawlike or throbbing, but it can although females are admittedly rarely affected). There sometimes be described as dental, boring, or pressing (1). was another trait that, upon scrutiny, did not seem to The pain has an abrupt onset and cessation. Roughly 50% be quite typical: there was a multitude of attacks per of patients prefer to sit or curl up in bed during attacks (1). 24h, i.e. up to 24 or more per day. Another remarkable Photophobia (21%), nausea (14%), and vomiting (2%) may feature was the intractability of the headache....Over be present (1). In one study, 27 of 31 patients asked noted the course of the following years, every feasible drug at least one migrainous feature of photophobia, nausea, or was tried on her. Prior to each admission, she had dis- vomiting during an attack (5). continued her usual drug (mainly acetylsalicylic acid) Ipsilateral autonomic features typically occur during at- which kept the attacks at a reasonable level. Each drug trial ended either with an absolutely negative response, tacks of pain. The most common symptoms are lacrima- or—more usually—with an adverse reaction. The latter tion and nasal congestion, but conjunctival injection, response pattern was so typical that for almost every rhinorrhea, forehead and facial sweating, eyelid edema, new drug that was tried she was brought from a stage ptosis, and miosis can also occur (1). Bilateral autonomic of moderate or weak attacks to a stage of incapacitat- symptoms can occur (1). Dissociation between pain and ing and excruciatingly severe attacks....Butshewould autonomic features can be seen (40). not give up the hope that there was a solution to her The headache usually lasts 10 to 30 minutes (mean 20.9 problem. And she was the one who motivated us to minutes), with a range from 2 to 120 minutes (1). The fre- try new approaches, not the other way around. . . . To quency ranges from 1 to 40 attacks per day, with a mean make matters even worse, she was diagnosed as being of 11 attacks per day (1). In 74 patients, the mean usual an hysterical person...despite the unilaterality of the duration was 26 minutes and the mean usual attack fre- pain, lacrimation, rhinorrhoea, etc.... “[T]he patient felt that everything centred on the quency was six (5). In a prospective study of 105 attacks in eye. . . . [W]e had arrived at a point where we were five patients, the mean duration was 13.3 minutes and the running out of arguments when trying to reject the mean frequency was 14 per day (49). Attacks often occur patient’s contention that an enucleation of the right regularly throughout the 24-hour period, without the pre- (symptomatic side) eye would perhaps solve her pain ponderance of nocturnal attacks typically seen in CH. Noc- problem. turnal attacks associated with rapid eye movement (REM) “Fortunately, the following developments took place sleep have been reported (26). Interictal discomfort or pain simultaneously. The patient had from the start claimed is present in up to one-third of patients (1). that salicylates seemed to give her some relief, not to Most attacks are spontaneous, but 10% of patients can the extent that the pain disappeared, but at times when trigger attacks with neck movement (1). Alcohol ingestion they were not maximal the paroxysms could be modi- triggers attacks in approximately 7% of patients (1). fied by salicylates. Perhaps the paroxysms became even more rare during such medication. We thought that a PH has chronic and episodic patterns, similar to CH. In lot of drugs would be more promising than salicylates contrast to CH, however, the chronic form of paroxysmal as potential therapeutic agents. The anti-inflammatory PH is more common than the episodic form, occurring in agents were therefore put rather far down on our list 80% of patients (1). Approximately 20% of patients with of potentially effective drugs worthy of trial....When PH have clear intervals between bouts of attacks (EPH). P1: KWW/KKL P2: KWW/HCN QC: KWW/FLX T1: KWW GRBT050-97 Olesen- 2057G GRBT050-Olesen-v6.cls August 17, 2005 1:30

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The duration of the headache phase in EPH ranges from 2 red ear syndrome has been described (6). CPH with aura weeks to 4.5 months (39). Remissions in EPH range from 1 has been reported (32). to 36 months (39). EPH has been reported to stay episodic for up to 35 years (1). EPH can evolve into typical CPH and vice versa. DIFFERENTIAL DIAGNOSIS PH has been observed in association with other primary headache disorders, including trigeminal neural- Numerous cases of secondary PH have been reported, un- gia (paroxysmal hemicrania–tic syndrome) (7,10), CH derlining the importance of magnetic resonance imaging (11), migraine (41), primary stabbing headache (62), and (MRI) of the brain in every case. Even cases ﬁtting all the primary cough headache (31). Typically, each type of criteria for CPH that respond completely to indomethacin headache requires a separate treatment (except when PH is can have a secondary etiology (5). Secondary causes of PH associated with primary cough headache or primary stab- are listed in Table 97-1. bing headache). The number one differential diagnosis for CPH is Unusual clinical features have been reported, includ- chronic CH, while EPH is most likely to be confused with ing side-alternating attacks (19,40,44), bilateral or center episodic CH. The female sex preponderance of PH is the of forehead pain (38,45), and absence of autonomic fea- opposite of CH, but this is not helpful information when tures (6,8,44). Cases presenting with primarily ear pain confronted with the individual patient. PH differs from and a sensation of external acoustic meatus obstruction CH mainly in the higher frequency and shorter duration have been reported, and a case of CPH associated with the of individual attacks (Table 97-2). The mean usual attack

◗ TABLE 97-2 Clinical Features of the Trigeminal Autonomic Cephalalgias and Hemicrania Continua Paroxysmal Cluster Headache Hemicrania SUNCT Syndrome Hemicrania Continua

Sex F:M 1:2.5–7 2.36:1 1:1.3 2:1 Pain: Type Stabbing, boring Throbbing, boring, Burning, stabbing, sharp Background dull ache; stabbing throbbing/stabbing exacerbations Severity Excruciating Excruciating Severe Moderate background pain; severe exacerbations Site Orbit, temple Orbit, temple Periorbital Orbit, temple Attack frequency 1/alternate day–8/day 1–40/day (>5/day for 3–200/day Continuous more than half the time) Duration of 15–180 min 2–30 min 5–240 sec Continuous background attack pain; exacerbations variable, lasting minutes to days Autonomic YesYes Yes (prominent Yes (mainly with features conjunctival injection exacerbations; less and lacrimation) prominent than in other trigeminal autonomic cephalalgias) Migrainous Yes (photophobia may Yes (photophobia may Very rarely (photophobia Yes (during exacerbations) features∗ be lateralized to pain be lateralized to pain may be lateralized to side) side) pain side) Alcohol trigger Yes Occasional No Rare Indomethacin — ++ — ++ effect Abortive Sumatriptan injection Nil Nil Nil treatment Oxygen Prophylactic Verapamil Indomethacin Lamotrigine Indomethacin treatment Lithium

*Nausea, photophobia, or phonophobia; ++ indicates absolute response to indomethacin. From (33). P1: KWW/KKL P2: KWW/HCN QC: KWW/FLX T1: KWW GRBT050-97 Olesen- 2057G GRBT050-Olesen-v6.cls August 17, 2005 1:30

820 Tension-Type Headaches, Cluster Headaches, and Other Primary Headaches

duration of PH is 26 minutes (5), while the mean usual is suspected, an indomethacin trial should be performed. attack duration of CH is approximately 60 minutes (27). The trial dosage of indomethacin should be increased to The mean usual attack frequency of PH is six (5), while at least 150 mg per 24 hr for 3 to 4 days. The beneficial the usual attack frequency of CH is one (30). There is con- effect is seen within 48 hours (a few hours to 5 days). Six siderable overlap in these characteristics, however. For ex- out of 11 CPH patients became pain free within 7 hours ample, although the usual attack frequency in a series of after indomethacin, and in only one the time before relief 74 patients was six, 63% of patients had a usual attack fre- was greater than 24 hours (42). The maintenance dosage is quency in 24 hours of less than six, and if one were only usually 25 to 100 mg per day but may vary inter- and in- looking for PH in patients with a high frequency of daily traindividually between 12.5 and 300 mg/day, depending attacks, some cases of PH would be missed (5). Sophis- on the fluctuation in attack severity (55). On discontin- ticated instrumental examinations such as evaporimetry, uation, symptoms usually reappear within 12 hours to a pupillometry, and dynamic tonometry can detect differ- few days (1 to 14 days) (63). However, long-lasting re- ences between PH and CH sufferers (57), but such inves- mission periods up to years have been described (24). tigations are not frequently available to most physicians. Indomethacin requirements usually vary with time, and PH responds dramatically to indomethacin, while the ev- many patients find that the minimum effective dose varies idence for the efficacy of indomethacin in CH is minimal from one moment to the next. and anecdotal (4). Since PH and CH can be clinically in- In about 10% of cases indomethacin side effects are ex- distinguishable, any patient presenting with what appears pected (1). The potentially most serious side effects of in- to be CH should have an indomethacin trial, especially if domethacin are dyspepsia and the development of a bleed- attacks have been refractory to usual CH treatments. ing peptic ulcer. Antacids, H2 blockers, or proton-pump Short-lasting paroxysmal hemicrania must also be dif- inhibitors should be considered when indomethacin is be- ferentiated from SUNCT syndrome (Table 97-2). In PH the ing given over longer periods. Nausea, vomiting, vertigo, attacks have a uniform distribution throughout the day and purpura have also been reported during indomethacin and night and the triggers are different than those seen in use (1). Suppositories of indomethacin may help if gastric SUNCT (33). PH attacks abate with indomethacin, which intolerance is a major problem, or when the dose even- is not effective in SUNCT. Some patients with PH com- tually needs to be increased up to higher doses, such as plain of a dull interictal pain in their usual attack location 300 mg per day. between attacks (33). These patients are usually differen- tiated clinically from hemicrania continua on the basis of the temporal profile of the attacks and the associated fea- Other Drugs tures (Table 97-2). The exacerbations in hemicrania con- Verapamil and acetylsalicylic acid may give partial relief, tinua are longer lasting and have less robust autonomic especially in the early stages of PH (15). Two out of six features than the attacks seen in CH, paroxysmal hemicra- CPH patients obtained complete relief with piroxicam β- nia, and SUNCT. cyclodextrin, and one had moderate relief (60). There are reports on the effectiveness of celecoxib and rofecoxib in PROGNOSIS PH (29,34). Since PH attacks are relatively short, test- ing the effect of acute drugs may be particularly difficult. However, except in some reports (15,19), sumatriptan and The natural history of PH is largely unknown. In a review oxygen are considered ineffective. The effect of prophylac- of all the reported cases in 1989, the mean duration of tic drugs is better tested in chronic cases, since an even- illness was 13.3 ± 12.2 years (1). It seems to be a life- tual “response” may correspond to the natural fluctuation long condition, although EPH can transform into CPH and of the disease. Anecdotal reports on the efficacy of var- vice versa. Patients typically do not develop tachyphylaxis ious drugs may be related to inobservance of this fact. to indomethacin. Many patients can decrease the dose of Lithium, carbamazepine, and other anticonvulsants are indomethacin required to maintain a pain-free state over ineffective. Anesthetic blockades of the greater occipital time (43). nerve, supraorbital nerve, and minor occipital nerve are ineffective (3). MANAGEMENT Surgical and Nonpharmacologic The treatment of PH is entirely prophylactic, as attacks Treatment are too short and intense for any acute oral treatment to be effective. Indomethacin is the drug of choice and must There is no evidence of efficacy of surgical treatment, chi- have an absolute effect on the symptoms, provided the dose ropractic manipulation, acupuncture, or other alternative is sufficient for that particular individual (4). When PH options for the treatment of PH. 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